Coxiella burnetii is an intracellular pathogen that causes the human disease Q-fever. Mechanisms by which this bacterial pathogen exploits human cells remain unknown. This project is focused on identifying key virulence determinants in Coxiella and determining how these factors promote infection. The Coxiella Dot/Icm system is a functional protein secretion machine that promotes infection by delivering bacterial effectors into host cells. We have identified Coxiella effector proteins and host proteins important for infection. To understand the interface between these bacterial determinants and host proteins the following specific aims will be completed. Aim 1) Identify Coxiella effectors and host factors required for infection using genome-wide screening approaches. Aim 2) Determine the role of the Coxiella Dot/Icm system during infection and identify bacterial determinants required for intracellular replication. Aim 3) Elucidate the function of Coxiella effectors.